SRSF2

Primary Author(s)*

Paul De Fazio, MSc, Monash Health

Synonyms

• Splicing Factor, Arginine/Serine-Rich 2
• Serine And Arginine Rich Splicing Factor 2
• Splicing Component, 35 KDa
• Splicing Factor SC35
• SC35

Genomic Location

Cytoband: 17q25.1

Genomic Coordinates:

chr17:74,730,197-74,733,493 [hg19]

chr17:76,734,115-76,737,629 [hg38]

Cancer Category/Type

Myelodysplastic Syndromes (MDS)

SRSF2 is mutated in approximately 14% of MDS patients (Papaemmanuil et al., 2013). SRSF2 variants are mutually exclusive to EZH2 variants, SF3B1 variants, and pathogenic variants in other splicing factors, but are positively correlated with IDH1, IDH2, and RUNX1 mutations (Papaemmanuil et al., 2013; Thol et al., 2012; Yoshida et al., 2011). SRSF2 variants typically originate early in the generation of dysplastic lineages (Papaemmanuil et al., 2013). SRSF2 variants correlate with shorter overall survival and more frequent progression to acute myeloid leukemia (AML) (Thol et al., 2012). These variants are almost always missense mutations in proline residue 95 (NM_003016.4) (Yoshida et al., 2011).

Chronic Myelomonocytic Leukemia (CMML)

SRSF2 variants, predominantly missense mutations affecting the proline 95 (NM_003016.4) residue, are seen in approximately 32-47% of chronic myelomonocytic leukemia (CMML) cases but rarely in juvenile myelomonocytic leukemia (Kar et al., 2013; Meggendorfer et al., 2012). SRSF2 variants are positively correlated with higher age, less pronounced anemia, and a normal karyotype. The prognostic impact is unclear, although SRSF2 and RUNX1 co-mutation may correlate with an improved overall survival (Itzykson et al., 2013; Meggendorfer et al., 2012). EZH2 and SRSF2 variants are mutually exclusive (Meggendorfer et al., 2012).

Acute Myeloid Leukemia (AML) and Related Precursor Neoplasms

Mutations in SRSF2, mostly affecting proline 95 (NM_003016.4), are found in ~7% of acute myeloid leukemia (AML) with myelodysplasia-related changes but rarely (<1%) in patients with de novo AML (Yoshida et al., 2011). One study found that SRSF2 variants correlated with older age but no other prognostic markers in AML; however, AML sub-types were not separated (Yang et al., 2016).

Gene Overview

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Common Alteration Types

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Copy Number Loss	Copy Number Gain	LOH	Loss-of-Function Mutation	Gain-of-Function Mutation	Translocation/Fusion
EXAMPLE: X	EXAMPLE: X	EXAMPLE: X	EXAMPLE: X	EXAMPLE: X	EXAMPLE: X

Internal Pages

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EXAMPLE Germline Cancer Predisposition Genes

External Links

Put your text here - Include as applicable links to: 1) Atlas of Genetics and Cytogenetics in Oncology and Haematology, 2) COSMIC, 3) CIViC, 4) St. Jude ProteinPaint, 5) Precision Medicine Knnowledgebase (Weill Cornell), 6) Cancer Index, 7) OncoKB, 8) My Cancer Genome, 9) UniProt, 10) Pfam, 11) GeneCards, 12) GeneReviews, and 13) Any gene-specific databases.

EXAMPLES

TP53 by Atlas of Genetics and Cytogenetics in Oncology and Haematology - detailed gene information

TP53 by COSMIC - sequence information, expression, catalogue of mutations

TP53 by CIViC - general knowledge and evidence-based variant specific information

TP53 by IARC - TP53 database with reference sequences and mutational landscape

TP53 by St. Jude ProteinPaint mutational landscape and matched expression data.

TP53 by Precision Medicine Knowledgebase (Weill Cornell) - manually vetted interpretations of variants and CNVs

TP53 by Cancer Index - gene, pathway, publication information matched to cancer type

TP53 by OncoKB - mutational landscape, mutation effect, variant classification

TP53 by My Cancer Genome - brief gene overview

TP53 by UniProt - protein and molecular structure and function

TP53 by Pfam - gene and protein structure and function information

TP53 by GeneCards - general gene information and summaries

GeneReviews - information on Li Fraumeni Syndrome

References

EXAMPLE Book

1. Arber DA, et al., (2008). Acute myeloid leukaemia with recurrent genetic abnormalities, in World Health Organization Classification of Tumours of Haematopoietic and Lymphoid Tissues, 4th edition. Swerdlow SH, Campo E, Harris NL, Jaffe ES, Pileri SA, Stein H, Thiele J, Vardiman JW, Editors. IARC Press: Lyon, France, p117-118.

EXAMPLE Journal Article

1. Li Y, et al., (2001). Fusion of two novel genes, RBM15 and MKL1, in the t(1;22)(p13;q13) of acute megakaryoblastic leukemia. Nat Genet 28:220-221, PMID 11431691.

Notes

*Primary authors will typically be those that initially create and complete the content of a page. If a subsequent user modifies the content and feels the effort put forth is of high enough significance to warrant listing in the authorship section, please contact the CCGA coordinators (contact information provided on the homepage). Additional global feedback or concerns are also welcome.